1. Field of the Invention
The recent development of myeloma-hybrid cell lines for producing immunospecific antibodies allows for the indefinite production of large quantities of homogeneous (monoclonal) antibody specific for a single antigenic determinant of an immunizing antigen, despite the overall heterogeneity of the antibody response to the antigen. Cloning and selecting lines with desired reactivities, however, is currently a laborious procedure that constitutes a major limitation to rapid establishment of a wide range of lines producing antibodies useful for research and medicine.
The current selection procedures rely on dispersion of cells in soft agar or on limiting dilution microculture for physical isolation of the hybrid clones after hybridization. Desired hybrids are identified by screening for production of antibody after clones grow. For many antigens not readily adapted to a plaque assay, such as protein antigens, allotypes and impure mixtures of naturally occurring antigens, culture supernates are assayed for antibody. There are practical limits to the number of individual culture supernates which may be screened. Furthermore, besides the difficulties in screening large number of isolates to find the desired clone(s), there is the further difficulty that overgrowth of the culture by unwanted clones or nonproducing variants may obscure the desired clone.
It is therefore desirable that a rapid, accurate and efficient method be provided for screening large numbers of cells, either existing individually or as part of a clone, for isolating one or more hybridoma cells producing the desired antibody.
2. Description of the Prior Art
Parks et al., PNAS USA (1979) 76, 1962-1966 describes the subject process and its disclosure is incorporated herein by reference. Of interest to the background of the subject invention are the references cited therein.